The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
AMP-Activated Protein Kinase Protects Cardiomyocytes against Hypoxic Injury through Attenuation of Endoplasmic Reticulum Stress
Open accessAbstract
Oxygen deprivation leads to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), causing ER stress. Under conditions of ER stress, inhibition of protein synthesis and up-regulation of ER chaperone expression reduce the misfolded proteins in the ER. AMP-activated protein kinase (AMPK) is a key regulatory enzyme involved in energy homeostasis during hypoxia. It has been shown that AMPK activation is associated with inhibition of protein synthesis via phosphorylation of elongation factor 2 (eEF2) in cardiomyocytes. We therefore examined whether AMPK attenuates hypoxia-induced ER stress in neonatal rat cardiomyocytes. We found that hypoxia induced ER stress, as assessed by the expression of CHOP and BiP and cleavage of caspase 12. Knockdown of CHOP or caspase 12 through small interfering RNA (siRNA) resulted in decreased expression of cleaved poly(ADP-ribose) polymerase following exposure to hypoxia. We also found that hypoxia-induced CHOP expression and cleavage of caspase 12 were significantly inhibited by pretreatment with 5-aminoimidazole-4-carboxyamide-1-beta-D-ribofuranoside (AICAR), a pharmacological activator of AMPK. In parallel, adenovirus expressing dominant-negative AMPK significantly attenuated the cardioprotective effects of AICAR. Knockdown of eEF2 phosphorylation using eEF2 kinase siRNA abolished these cardioprotective effects of AICAR. Taken together, these findings demonstrate that activation of AMPK contributes to protection of the heart against hypoxic injury through attenuation of ER stress and that attenuation of protein synthesis via eEF2 inactivation may be the mechanism of cardioprotection by AMPK.
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Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
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Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
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The AMP‐Activated Protein Kinase: Fuel Gauge of the Mammalian Cell?
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Orchestrating the unfolded protein response in health and disease
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Adiponectin-mediated modulation of hypertrophic signals in the heart
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Cited by
Salminen, A., Hyttinen, J. M. T., & Kaarniranta, K. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0748-0 · Cited by 866
Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition
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Resveratrol stimulates AMP kinase activity in neurons
Dasgupta, B., & Milbrandt, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610068104 · Cited by 723
Kalogeris, T., Baines, C. P., Krenz, M., & Korthuis, R. J. (2016) · Comprehensive Physiology · doi:10.1002/cphy.c160006 · Cited by 718
Santos, C. X. C., Tanaka, L. Y., Wosniak, J., & Laurindo, F. R. M. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2625 · Cited by 572
Metadata
- Authors
- Terai, K., Hiramoto, Y., Masaki, M., Sugiyama, S., Kuroda, T., Hori, M., Kawase, I., & Hirota, H.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-11-01
- Volume
- 25
- Issue
- 21
- Pages
- 9554-9575
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2161980140
- Cited by
- 352
- References
- 13
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- green
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- Terai, K., Hiramoto, Y., Masaki, M., Sugiyama, S., Kuroda, T., Hori, M., Kawase, I., & Hirota, H. (2005). AMP-Activated Protein Kinase Protects Cardiomyocytes against Hypoxic Injury through Attenuation of Endoplasmic Reticulum Stress. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.25.21.9554-9575.2005
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